Tissue engineering involves assembling cells and their support structures together to restore normal function of diseased or damaged tissue (Langer, R. & Vacanti, J. P. Tissue Engineering. Science 260, 920-926 (1993)). Supplying sufficient oxygen to the engineered tissue is essential for survival and integration of transplanted cells otherwise necrosis occurs. However, limitations of oxygen diffusion has led to a general conception that cell or tissue components may not be implanted in large volumes (Folkman, J. & Hochberg, M. J Exp Med 138, 745-53 (1973)).
Numerous efforts have been made to overcome this limitation, which include the use of oxygen rich fluids such as perfluorocarbons and silicone oils (Radisic, M. et al. Biomimetic approach to cardiac tissue engineering: Oxygen carriers and channeled scaffolds. Tissue Engineering 12, 2077-2091 (2006); Leung, R., Poncelet, D. & Neufeld, R. J. Enhancement of oxygen transfer rate using microencapsulated silicone oils as oxygen carriers. Journal of Chemical Technology and Biotechnology 68, 37-46 (1997)).
Other approaches to maintaining tissue viability attempted include the use of angiogenic factors, such as vascular endothelial growth factors (VEGF) and endothelial cells, and cell-support matrices that permit enhanced diffusion across the entire implant (De Coppi, P. et al. Tissue Eng 11, 1034-44 (2005); Kaigler, D. et al., J Bone Miner Res 21, 735-44 (2006); Nomi, M. et al., J. Natl. Cancer Inst. 93, 266-267 (2001).
However, the use of oxygen rich fluids and angiogeneic factors have only partially succeeded in achieving survival of a clinically applicable large tissue mass.